Anis A Hamid1, Kathryn P Gray2, Ying Huang3, Michaela Bowden1, Mark Pomerantz1, Massimo Loda3, Christopher J Sweeney4. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 2. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. 3. Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. 4. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: christopher_sweeney@dfci.harvard.edu.
Abstract
BACKGROUND: PTEN deletion is associated with relapse after therapy for localized prostate cancer. There are limited data on PTEN loss as detected by immunohistochemistry (IHC) and the risk of lethal disease after surgery. OBJECTIVE: To determine whether PTEN loss as detected by quantitative fluorescence IHC (FIHC) predicts lethal disease outcomes after surgery for prostate cancer. DESIGN, SETTING AND PARTICIPANTS: We used formalin-fixed, paraffin-embedded radical prostatectomy specimens to construct tissue microarrays and perform dual FIHC for PTEN and AMACR for masking tumor epithelium, plus semi-quantitative multispectral imaging analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association of PTEN status analyzed continuously and dichotomously (low [expression in the lowest quartile] vs higher [expression >lowest quartile]) with disease outcomes (metastasis and death) was assessed with adjustment for age, Gleason score, and stage in multivariable analyses. The prognostic ability of PTEN was assessed using logistic regression models. RESULTS AND LIMITATIONS: Low PTEN expression was associated with a higher risk of metastatic disease as both a continuous (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.14-1.92; p<0.003) and dichotomous (HR 1.92, 95% CI 1.02-3.63; p=0.04) variable. A significant association between low PTEN expression and poorer overall survival was observed (continuous: HR 1.89, 95% CI 1.37-2.63; p<0.001; dichotomous: HR 2.66, 95% CI 1.34-5.28; p=0.005). Addition of PTEN status to clinicopathologic factors (age, Gleason score, and stage) incrementally improved a prognostic model assessing 10-yr outcomes for metastatic disease (area under the curve [AUC] 0.76 vs 0.80) and death (AUC 0.70 vs 0.75). CONCLUSIONS: Low PTEN expression detected by FIHC in primary prostate cancer is an independent prognostic biomarker for metastatic disease and death after definitive therapy. FIHC for PTEN is a viable clinical diagnostic assay in this context. PATIENT SUMMARY: We looked at loss of the PTEN protein in prostate tumors from men treated with surgery. Men with PTEN loss were at higher risk of metastasis and death. Assessing PTEN status may be useful in better determination of the risk of poorer outcomes.
BACKGROUND:PTEN deletion is associated with relapse after therapy for localized prostate cancer. There are limited data on PTEN loss as detected by immunohistochemistry (IHC) and the risk of lethal disease after surgery. OBJECTIVE: To determine whether PTEN loss as detected by quantitative fluorescence IHC (FIHC) predicts lethal disease outcomes after surgery for prostate cancer. DESIGN, SETTING AND PARTICIPANTS: We used formalin-fixed, paraffin-embedded radical prostatectomy specimens to construct tissue microarrays and perform dual FIHC for PTEN and AMACR for masking tumor epithelium, plus semi-quantitative multispectral imaging analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association of PTEN status analyzed continuously and dichotomously (low [expression in the lowest quartile] vs higher [expression >lowest quartile]) with disease outcomes (metastasis and death) was assessed with adjustment for age, Gleason score, and stage in multivariable analyses. The prognostic ability of PTEN was assessed using logistic regression models. RESULTS AND LIMITATIONS: Low PTEN expression was associated with a higher risk of metastatic disease as both a continuous (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.14-1.92; p<0.003) and dichotomous (HR 1.92, 95% CI 1.02-3.63; p=0.04) variable. A significant association between low PTEN expression and poorer overall survival was observed (continuous: HR 1.89, 95% CI 1.37-2.63; p<0.001; dichotomous: HR 2.66, 95% CI 1.34-5.28; p=0.005). Addition of PTEN status to clinicopathologic factors (age, Gleason score, and stage) incrementally improved a prognostic model assessing 10-yr outcomes for metastatic disease (area under the curve [AUC] 0.76 vs 0.80) and death (AUC 0.70 vs 0.75). CONCLUSIONS: Low PTEN expression detected by FIHC in primary prostate cancer is an independent prognostic biomarker for metastatic disease and death after definitive therapy. FIHC for PTEN is a viable clinical diagnostic assay in this context. PATIENT SUMMARY: We looked at loss of the PTEN protein in prostate tumors from men treated with surgery. Men with PTEN loss were at higher risk of metastasis and death. Assessing PTEN status may be useful in better determination of the risk of poorer outcomes.
Authors: Érica Romão Pereira; Laís Capelasso Lucas Pinheiro; Amanda Letícia Francelino; Carlos Alberto Miqueloto; Alda Fiorina Maria Losi Guembarovski; Karen Brajão de Oliveira; Paulo Emílio Fuganti; Ilce Mara de Syllos Cólus; Roberta Losi Guembarovski Journal: J Cancer Res Clin Oncol Date: 2022-08-25 Impact factor: 4.322
Authors: Piotr Zapała; Łukasz Fus; Zbigniew Lewandowski; Karolina Garbas; Łukasz Zapała; Barbara Górnicka; Piotr Radziszewski Journal: J Clin Med Date: 2021-11-27 Impact factor: 4.241
Authors: Konrad H Stopsack; Ying Huang; Svitlana Tyekucheva; Travis A Gerke; Clyde Bango; Habiba Elfandy; Michaela Bowden; Kathryn L Penney; Thomas M Roberts; Giovanni Parmigiani; Philip W Kantoff; Lorelei A Mucci; Massimo Loda Journal: Clin Cancer Res Date: 2020-09-10 Impact factor: 12.531
Authors: Adam B Weiner; Farzana A Faisal; Elai Davicioni; R Jeffrey Karnes; Donald J Vander Griend; Tamara L Lotan; Edward M Schaeffer Journal: Eur Urol Oncol Date: 2020-06-12
Authors: Sabina Luszczak; Benjamin S Simpson; Urszula Stopka-Farooqui; Vignesh Krishna Sathyadevan; Lina M Carmona Echeverria; Christopher Kumar; Helena Costa; Aiman Haider; Alex Freeman; Charles Jameson; Marzena Ratynska; Imen Ben-Salha; Ashwin Sridhar; Greg Shaw; John D Kelly; Hayley Pye; Kathy A Gately; Hayley C Whitaker; Susan Heavey Journal: Sci Rep Date: 2020-09-01 Impact factor: 4.379
Authors: Chaoran Ma; Ye Wang; Kathryn M Wilson; Lorelei A Mucci; Meir J Stampfer; Michael Pollak; Kathryn L Penney Journal: JNCI Cancer Spectr Date: 2021-12-15